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991.
Zhang D Fan GC Zhou X Zhao T Pasha Z Xu M Zhu Y Ashraf M Wang Y 《Journal of molecular and cellular cardiology》2008,44(2):281-292
Bone marrow mesenchymal stem cells (MSCs) participate in myocardial repair following myocardial infarction. However, their in vivo reparative capability is limited due to lack of their survival in the infarcted myocardium. To overcome this limitation, we genetically engineered male rat MSCs overexpressing CXCR4 in order to maximize the effect of stromal cell-derived factor-1α (SDF-1α) for cell migration and regeneration. MSCs were isolated from adult male rats and cultured. Adenoviral transduction was carried out to over-express either CXCR4/green fluorescent protein (Ad-CXCR4/GFP) or Ad-null/GFP alone (control). Flow cytometry was used to identify and isolate GFP/CXCR4 over-expressing MSCs for transplantation. Female rats were assigned to one of four groups (n = 8 each) to receive GFP-transduced male MSCs (2 × 106) via tail vein injection 3 days after ligation of the left anterior descending (LAD) coronary artery: GFP-transduced MSCs (Ad-null/GFP-MSCs, group 1) or MSCs over-expressing CXCR4/GFP (Ad-CXCR4/GFP-MSCs, group 2), or Ad-CXCR4/GFP-MSCs plus SDF-1α (50 ng/μl) (Ad-CXCR4/GFP-MSCs/SDF-1α, group 3), or Ad-miRNA targeting CXCR4 plus SDF-1α (Ad-miRNA/GFP-MSCs + SDF-1α treatment, group 4). Cardiodynamic data were obtained 4 weeks after induction of regional myocardial infarction (MI) using echocardiography after which hearts were harvested for immunohistochemical studies. The migration of GFP and Y-chromosome positive cells increased significantly in the peri- and infarct areas of groups 2 and 3 compared to control group (p < 0.05), or miRNA-CXCR4 group (p < 0.01). The number of CXCR4 positive cells in groups 2, 3 was intimately associated with angiogenesis and myogenesis. MSCs engraftment was blocked by pretreatment with miRNA (group 4). Cardiac function was significantly improved in rats receiving MSCs over-expressing CXCR4 alone or with SDF-1α. The up-regulation of matrix metalloproteinases (MMPs) by CXCR4 overexpressing MSCs perhaps facilitated their engraftment in the collagenous tissue of the infarcted area. CXCR4 over-expression led to enhance in vivo mobilization and engraftment of MSCs into ischemic area where these cells promoted neomyoangiogenesis and alleviated early signs of left ventricular remodeling. 相似文献
992.
We hypothesized that mesenchymal stem cells (MSCs) overexpressing insulin-like growth factor (IGF)-1 showed improved survival and engraftment in the infarcted heart and promoted stem cell recruitment through paracrine release of stromal cell-derived factor (SDF)-1alpha. Rat bone marrow-derived MSCs were used as nontransduced ((Norm)MSCs) or transduced with adenoviral-null vector ((Null)MSCs) or vector encoding for IGF-1 ((IGF-1)MSCs). (IGF-1)MSCs secreted higher IGF-1 until 12 days of observation (P<0.001 versus (Null)MSCs). Molecular studies revealed activation of phosphoinositide 3-kinase, Akt, and Bcl.xL and inhibition of glycogen synthase kinase 3beta besides release of SDF-1alpha in parallel with IGF-1 expression in (IGF-1)MSCs. For in vivo studies, 70 muL of DMEM without cells (group 1) or containing 1.5x10(6) (Null)MSCs (group 2) or (IGF-1)MSCs (group 3) were implanted intramyocardially in a female rat model of permanent coronary artery occlusion. One week later, immunoblot on rat heart tissue (n=4 per group) showed elevated myocardial IGF-1 and phospho-Akt in group 3 and higher survival of (IGF-1)MSCs (P<0.06 versus (Null)MSCs) (n=6 per group). SDF-1alpha was increased in group 3 animal hearts (20-fold versus group 2), with massive mobilization and homing of ckit(+), MDR1(+), CD31(+), and CD34(+) cells into the infarcted heart. Infarction size was significantly reduced in cell transplanted groups compared with the control. Confocal imaging after immunostaining for myosin heavy chain, actinin, connexin-43, and von Willebrand factor VIII showed extensive angiomyogenesis in the infarcted heart. Indices of left ventricular function, including ejection fraction and fractional shortening, were improved in group 3 as compared with group 1 (P<0.05). In conclusion, the strategy of IGF-1 transgene expression induced massive stem cell mobilization via SDF-1alpha signaling and culminated in extensive angiomyogenesis in the infarcted heart. 相似文献
993.
Muhammad Rashid Claire Lawson Jessica Potts Evangelos Kontopantelis Chun Shing Kwok Olivier Francois Bertrand Ahmad Shoaib Peter Ludman Tim Kinnaird Mark de Belder James Nolan Mamas A. Mamas 《JACC: Cardiovascular Interventions》2018,11(11):1021-1033
Objectives
The authors sought to determine the relationships between left radial access (LRA) or right radial access (RRA) and clinical outcomes using the British Cardiovascular Intervention Society (BCIS) database.Background
LRA has been shown to offer procedural advantages over RRA in percutaneous coronary intervention (PCI) although few data exist from a national perspective around its use and association with clinical outcomes.Methods
The authors investigated the relationship between use of LRA or RRA and clinical outcomes of in-hospital or 30-day mortality, major adverse cardiovascular events (MACE), in-hospital stroke, and major bleeding complications in patients undergoing PCI between 2007 and 2014.Results
Of 342,806 cases identified, 328,495 (96%) were RRA and 14,311 (4%) were LRA. Use of LRA increased from 3.2% to 4.6% from 2007 to 2014. In patients undergoing a repeat PCI procedure, the use of RRA dropped to 72% at the second procedure and was even lower in females (65%) and patients >75 years of age (70%). Use of LRA (compared with RRA) was not associated with significant differences in in-hospital mortality (odds ratio [OR]: 1.19, 95% confidence interval [CI]: 0.90 to 1.57; p = 0.20), 30-day mortality (OR: 1.17, 95% CI: 0.93 to 1.74; p = 0.16), MACE (OR: 1.06, 95% CI: 0.86 to 1.32; p = 0.56), or major bleeding (OR: 1.22, 95% CI: 0.87 to 1.77; p = 0.24). In propensity match analysis, LRA was associated with a significant decrease in in-hospital stroke (OR: 0.52, 95% CI: 0.37 to 0.82; p = 0.005).Conclusions
In this large PCI database, use of LRA is limited compared with RRA but conveys no increased risk of adverse outcomes, but may be associated with a reduction in PCI-related stroke complications. 相似文献994.
Cell growth, global phosphotyrosine elevation, and c-Met phosphorylation through Src family kinases in colorectal cancer cells 下载免费PDF全文
Emaduddin M Bicknell DC Bodmer WF Feller SM 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(7):2358-2362
The heterogeneity of cancer cell signaling is a significant obstacle for the effective development and clinical use of molecularly targeted therapies. As a contribution to a better understanding of the diversity of signaling activities in colorectal cancers (CRCs), we have analyzed the activity of Src family kinases (SFKs), which are implicated in human cancer development, in 64 CRC cell lines. A striking diversity of SFK activity was observed within this panel. Importantly, all CRC lines tested depend on SFK activity for their growth. In addition, SFK activity levels strongly correlated with global levels of tyrosine-phosphorylated (pTyr) proteins in CRC lines. SFK inhibition substantially reduced these pTyr levels, suggesting that SFKs may function as signal integration points and master controllers for the pTyr protein status in CRC lines. The majority of analyzed CRC lines with high-SFK activity express activated c-Met (pYpY1234/1235), a receptor tyrosine kinase contributing to the regulation of cell proliferation, migration, and invasion. Inhibition of SFKs reduced c-Met phosphorylation in most cases, indicating a reversed signal flow from SFK to c-Met. We conclude that SFK activity is important for the growth of CRC lines, although only low activity levels are required. If this also is true for CRC patients, tumors with low-SFK activity may be particularly sensitive to SFK inhibitors, and such patients should be targeted in clinical trials testing SFK inhibitors. 相似文献
995.
996.
Mortality and Readmission Rates in Patients Hospitalized for Acute Decompensated Heart Failure: A Comparison Between Cardiology and General‐Medicine Service Outcomes in an Underserved Population 下载免费PDF全文
997.
998.
Comparison of acute elastic recoil between the SAPIEN‐XT and SAPIEN valves in transfemoral–transcatheter aortic valve replacement 下载免费PDF全文
Shikhar Agarwal MD MPH Olcay Aksoy MD Muhammad Hammadah MD Kanhaiya Lal Poddar MD Rishi Puri MD Lars G. Svensson MD PhD Amar Krishnaswamy MD E. Murat Tuzcu MD FACC Samir R. Kapadia MD FACC 《Catheterization and cardiovascular interventions》2015,85(3):490-496
- Complex arch anatomy (type 2, type 3) and bovine configuration were identified in 34.4% and 20.5% of carotid stent patients, respectively.
- Catheter manipulation time (CMT), rather than arch complexity per se, was the only independent predictor of adverse events after carotid stenting.
- Careful attention to patient selection, preprocedural planning, and stent technique are important to ensure success.
999.
Predictors and clinical implications of atrial fibrillation in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation 下载免费PDF全文
1000.